Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Process for preparing heterocyclic indene analogs

a heterocyclic indene and analog technology, applied in the field of new heterocyclic indene analog preparation process, can solve the problems of high high temperature and achieve the effect of low catalyst loading and modest selectivity, and high catalyst loading and selectivity

Inactive Publication Date: 2007-01-30
F HOFFMANN LA ROCHE INC
View PDF3 Cites 15 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0028]A more favored process is where the cyclocarbonylating is carried out in the presence of a base selected from the group consisting of tri-alkyl-amines, di-alkyl-aryl-amines, pyridines, alkyl-N-piperidines, sodium hydroxide, potassium hydroxide and salts of carbonic acids. An anhydride of the formula (R4(C═O))2O, wherein R4 is as defined as above is used. In addition, a catalyst comprising a transition metal compound and a ligand is provided. The transition metal compound is selected from the group consisting of Pd(OAc)2, Pd2dba3, PdCl2, Pd2Cl2(π-al

Problems solved by technology

These processes are characterized by high temperatures, high catalyst loadings and modest selectivity.
Moreover, the educts necessary for the reactions in these processes are expensive, since they have to be prepared by lengthy procedures, and are not available commercially.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Process for preparing heterocyclic indene analogs
  • Process for preparing heterocyclic indene analogs
  • Process for preparing heterocyclic indene analogs

Examples

Experimental program
Comparison scheme
Effect test

example 1

1-(1-Benzenesulfonyl-1H-indol-2-yl)-allyl Alcohol

[0136]10.3 g (40 mmol) of 1-(phenylsulfonyl)indole (synthesized analogous to T. Sakamoto; Y. Kondo; N. Takazawa; H. Yamanaka; J. Chem.Soc.Perkin Trans. 1; 16; 1996; 1927–1934) in 110 ml tetrahydrofuran were cooled to −20° C. To the stirred solution 30 ml of 1.6 M n-butyllithium were added at −20° C. within 20 min. The resulting suspension was warmed to 10° C. and stirred at 10° C. for 4 hours. The mixture was again cooled to −20° C. and a solution of 3.4 g acrolein (61 mmol) in 20 ml THF was added dropwise within 20 min at −20° C. The solution was stirred at 20° C. for 16 hours. 150 ml water was added dropwise, the mixture was vigorously stirred for 10 min. The phases were separated, and the water phase was extracted with 3×100 ml of methyl-t-butyl-ether. The combined organic phases were washed with 100 ml of brine, dried on sodium sulfate and rotary evaporated (35° C., 20 mbar). The residue was purified by liquid chromatography (elue...

example 2

Acetic Acid 1-(1-benzenesulfonyl-1H-indol-2-yl)-allyl Ester

[0139]To a solution of 19.1 g of 1-(1-benzenesulfonyl-1H-indol-2-yl)-allyl alcohol (74 mmol) in 244 ml dichloromethane were added 34 ml triethylamine and 0.7 g 4-dimethyl-aminopyridine. The solution was cooled to 3° C. To the magnetically stirred solution 23.5 ml of acetic anhydride qas added with a dropping funnel at a temperature below 5° C. The reaction mixture was stirred 2 h at 22° C. After cooling in an ice bath 250 ml of water was added at a temperature of 20 to 24° C. The mixture was vigorously stirred for 10 min. The phases were separated, and the water solution extracted with 250 ml of dichloromethane. The combined organic phases were extracted with 250 ml of water three times, and once with 250 ml of brine. The dichloromethane solution was dried on sodium sulfat and finally rotary evaporated (35° C., 50 mbar), yield 22.8 g. In the next step (the cyclocarbonylation) the resulting oil was used without purification (...

example 3

Benzoic Acid 1-(1-benzenesulfonyl-1H-indol-2-yl)-allyl Ester

[0141]To a stirred solution of 10.0 g of 1-(1-benzenesulfonyl-1H-indol-2-yl)-allyl alcohol (32 mmol) in 100 ml of pyridine were added dropwise 5.6 ml benzoyl chloride (48 mmol) at 10° C. The mixture was stirred for an additional 1 h at 20° C. Most of the pyridine was distilled off, the residue was given in portions to 300 ml of ice water. The pH was adjusted to 2–3 with conc. HCl. The water was distilled off and the residue was dissolved in 100 ml of diethyl ether. After about 1 h the product crystallized. The suspension was stirred in an ice bath for 2 h, the solid was filtered off. The crude material was recrystallized from 90 ml methanol and dried 12 h at 35° C.

[0142]Yield: 5.2 g (39%) HPLC 98.4 Area-%, m.p. 112–114° C.

[0143]1H NMR (δ, DDMSO): 7.19 (CH—O, d), 6.35 (CH═CH2, ddd), 5.44 (CH═CH2, dd), 5.48 (CH═CH2, dd), aromatic signals at 7.0–8.1.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

A process for the preparation heterocyclic indene analogs, especially with the preparation of 4-hydroxycarbazole or N-protected 4-hydroxycarbazole, involves cyclocarbonylation followed by saponification. This process avoids high temperatures and high catalyst loadings.

Description

[0001]This application is a divisional of U.S. patent application Ser. No. 10 / 054,462, filed Jan. 22, 2002, now U.S. Pat. No. 6,777,559.BACKGROUND OF THE INVENTION[0002]1. Field[0003]The present invention is concerned with a novel process for the preparation of heterocyclic indene analogs, especially with the preparation of 4-hydroxycarbazole or N-protected 4-hydroxycarbazole. These compounds may be used as a building block for pharmaceutically active compounds, e.g. 1-(9H-carbazol-4-yloxy)-3-[[2-(2-methoxy -phenoxy)ethyl]amino]-2-propanol (carvedilol). This compound is known in the art and is described for example in EP 0 004920. It is especially useful for prophylaxis and treatment of heart- and circulatory diseases like, for example, hypertension, coronary heart failure, angina pectoris and the like.[0004]2. Description[0005]Processes for the catalytic cyclocarbonylation of pyrrole and indole derivatives have been described by Hiday et al., Advances in Metal-Organic Chemistry, Vo...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D209/88C07B61/00C07D209/12C07D405/12
CPCC07D209/12C07D405/12C07D209/88
Inventor SCALONE, MICHELANGELOZEIBIG, THOMAS ALBERT
Owner F HOFFMANN LA ROCHE INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com